Histologic injury caused by recurrent hepatitis C virus (HCV) has been reported in up to 90% of HCV-infected patients who undergo liver transplantation with a cadaveric graft. However, the natural history of HCV after living donor liver transplantation (LDLT) is not well described. We performed a retrospective analysis of 68 consecutive HCV-infected adult patients: 45 recipients of cadaveric grafts (CAD) were compared with 23 LDLT patients. Elevated serum transaminases, positive HCV RNA, and liver biopsy consistent with histologic evidence of HCV defined recurrence. When comparing CAD with LDLT, both the incidence of HCV recurrence and time to recurrence were not different. The overall incidence of severe sequelae of HCV recurrence, either cholestatic hepatitis, grade III-IV inflammation, and/or HCV-induced graft failure requiring retransplantation, was also not different when comparing CAD with LDLT. However, when comparing CAD versus LDLT, no CAD patient developed cholestatic hepatitis C, compared with 17% of LDLT who developed this complication (P ؍ .001). Thus, in this patient population, the timing and incidence of HCV recurrence were not different when comparing CAD versus LDLT, but the incidence of cholestatic hepatitis was significantly greater in patients with HCV who underwent LDLT. (Liver Transpl 2003;9:1028-1035.) E nd stage liver disease caused by hepatitis C virus (HCV) is the most common indication for liver transplantation in the United States. However, complications caused by recurrent HCV infection are increasingly being recognized; in patients with active HCV replication before transplantation, reacquisition of viremia after transplantation is universal, and allograft hepatitis caused by HCV occurs in up to 90% of patients followed for 5 years. 1-9 Although histologic injury in the allograft caused by HCV is exceedingly common, disease progression after the development of hepatitis is variable, with some patients experiencing indolent disease and others rapidly progressing to cirrhosis and liver failure. In patents who develop HCV-associated cirrhosis posttransplantation, rapid decompensation is a common occurrence. It has been reported that up to 42% of patients with HCV-associated cirrhosis posttransplantation develop decompensation manifested as ascites, encephalopathy, or hepatic hydrothorax, and fewer than 50% of patients survive more than 1 year after the development of decompensation. 10-12 Thus, both prospective and retrospective data are emerging that indicate that the progression of HCV after orthotopic liver transplantation is accelerated when compared with nontransplantation patients. This has been attributed to multiple factors, including the impact of immunosuppression on viral replication and host defenses. 13 Several lines of anecdotal evidence suggest that HCV recurrence might be more severe in recipients of living donor liver transplantation (LDLT). We hypothesize that postoperative liver regeneration in the partial graft procured from living donors may facilitate HCV repli...
Key Points: 1. Hepatitis C is a global health problem affecting over 170 million people worldwide. 2. There is wide geographic variation in both prevalence and genotype distribution of hepatitis C virus on a global level. 3. Most hepatitis C virus is spread parenterally, either through intravenous drug use or, in lesser-developed countries, through blood contamination during medical procedures. 4. Hepatitis C is a leading cause of end-stage liver disease and hepatocellular carcinoma. 5. Despite a declining incidence of new infections, the burden of disease, both in terms of mortality and in terms of cost, is expected to increase over the next decade. (Liver Transpl 2003;9:S10-S13.)
Severe alcoholic hepatitis (sAH) is associated with a poor prognosis. There is no proven effective treatment for sAH, which is why early transplantation has been increasingly discussed. Hepatoblastoma‐derived C3A cells express anti‐inflammatory proteins and growth factors and were tested in an extracorporeal cellular therapy (ELAD) study to establish their effect on survival for subjects with sAH. Adults with sAH, bilirubin ≥8 mg/dL, Maddrey's discriminant function ≥ 32, and Model for End‐Stage Liver Disease (MELD) score ≤ 35 were randomized to receive standard of care (SOC) only or 3‐5 days of continuous ELAD treatment plus SOC. After a minimum follow‐up of 91 days, overall survival (OS) was assessed by using a Kaplan‐Meier survival analysis. A total of 203 subjects were enrolled (96 ELAD and 107 SOC) at 40 sites worldwide. Comparison of baseline characteristics showed no significant differences between groups and within subgroups. There was no significant difference in serious adverse events between the 2 groups. In an analysis of the intent‐to‐treat population, there was no difference in OS (51.0% versus 49.5%). The study failed its primary and secondary end point in a population with sAH and with a MELD ranging from 18 to 35 and no upper age limit. In the prespecified analysis of subjects with MELD < 28 (n = 120), ELAD was associated with a trend toward higher OS at 91 days (68.6% versus 53.6%; P = .08). Regression analysis identified high creatinine and international normalized ratio, but not bilirubin, as the MELD components predicting negative outcomes with ELAD. A new trial investigating a potential benefit of ELAD in younger subjects with sufficient renal function and less severe coagulopathy has been initiated. Liver Transplantation 24 380–393 2018 AASLD.
Our preliminary data demonstrate that DAAs can be used safely and effectively in patients after kidney transplantation. Patients with proteinuria or lower GFR should be monitored more closely.
Adolescents and adults with inherited disorders of coagulation have one of the highest prevalence rates of hepatitis C among known risk groups. Few data are available on the use of combination therapy with interferon and ribavirin in this population. Patients 13 years of age and older who were positive for hepatitis C virus (HCV) RNA by polymerase chain reaction and negative for human immunodeficiency virus were randomized to receive interferon alfa-2b (3 million units 3 times a week) plus ribavirin (1,000 mg/day) or interferon alfa-2b alone for 48 weeks with 24 weeks of posttreatment follow-up. Patients started on interferon alone who remained positive for HCV RNA at week 12 crossed over to treatment with interferon plus ribavirin. A total of 113 patients were treated. Thirty-seven patients were younger than 18 years. At the end of treatment, 18 of 56 (32%) treated with interferon plus ribavirin and 6 of 57 (11%) treated with interferon alone were negative for HCV RNA (P ؍ .005). Sustained virologic response in the combination arm was 29% (16 of 56) compared with 7% (4 of 57) for those started on interferon alone (P ؍ .027). Among adolescents younger than 18 years who were treated with combination therapy, 10 of 17 (59%) had sustained response compared with 6 of 39 (15%) of adult patients on the same regimen (P ؍ .001). In conclusion, in this U.S. multicenter, randomized trial of therapy for HCV in patients with inherited bleeding disorders, sustained virologic response rate was significantly improved for patients treated with interferon and ribavirin compared with those started on interferon alone. Adolescents treated with combination therapy had a significantly higher sustained response than adults did on the same regimen. (HEPATOLOGY 2002;36:967-972.)
The baseline prevalence of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) coinfection among 2705 patients enrolled in HIV clinical trials in the Community Programs for Clinical Research on AIDS (CPCRA) was 16.6%. For men, multivariate logistic regression showed that the baseline prevalence of HIV-HCV coinfection was positively associated with history of injection drug use, older age, antiretroviral therapy naive status, African American or Latino ethnicity, and no history of having sex with men. No association was found with baseline CD4+ cell count or HIV RNA level. The prevalence of HCV coinfection in a diverse HIV clinical trials cohort provides additional information about risk behaviors and demographic factors that can be used in the analysis of clinical and virologic outcomes.
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